Lammirato Andrea, Patsch Katherin, Feiereisen Fabien, Maly Karl, Nofziger Charity, Paulmichl Markus, Hackl Hubert, Trajanoski Zlatko, Valovka Taras, Huber Lukas A, Vietor Ilja
Division of Cell Biology, Biocenter, Medical University Innsbruck, Innrain 80-82, A-6020, Innsbruck, Austria.
Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innrain 80-82, A-6020, Innsbruck, Austria.
BMC Biol. 2016 Oct 25;14(1):95. doi: 10.1186/s12915-016-0318-6.
TPA Induced Sequence 7 acts as a transcriptional co-regulator controlling the expression of genes involved in differentiation of various cell types, including skeletal myoblasts. We and others have shown that TIS7 regulates adult myogenesis through MyoD, one of the essential myogenic regulatory factors.
Here, we present data identifying ICln as the specific, novel protein downstream of TIS7 controlling myogenesis. We show that TIS7/ICln epigenetically regulate myoD expression controlling protein methyl transferase activity. In particular, ICln regulates MyoD expression via its interaction with PRMT5 by an epigenetic modification that utilizes symmetrical di-methylation of histone H3 on arginine 8. We provide multiple evidences that TIS7 directly binds DNA, which is a functional feature necessary for its role in transcriptional regulation.
We present here a molecular insight into TIS7-specific control of MyoD gene expression and thereby skeletal muscle differentiation.
TPA诱导序列7作为一种转录共调节因子，控制包括骨骼肌成肌细胞在内的多种细胞类型分化相关基因的表达。我们和其他人已经表明，TIS7通过MyoD（一种重要的成肌调节因子）调节成年肌生成。
在此，我们展示了确定ICln为TIS7下游控制肌生成的特异性新蛋白的数据。我们表明，TIS7/ICln通过控制蛋白质甲基转移酶活性，在表观遗传上调节MyoD表达。特别是，ICln通过利用精氨酸8上组蛋白H3的对称二甲基化的表观遗传修饰，经由其与PRMT5的相互作用调节MyoD表达。我们提供了多个证据表明TIS7直接结合DNA，这是其在转录调控中发挥作用所必需的功能特征。
我们在此展示了对TIS7对MyoD基因表达及由此对骨骼肌分化的特异性控制的分子见解。
